Pharmaceutical significance of the cyclic imide form of recombinant human glial cell line derived neurotrophic factor

Purpose. The purpose of this paper is to determine the significance of cycl ic imide formation of an aspartic acid residue during storage on the pharma ceutical quality of a recombinant human glial cell line-derived neurotrophi c factor (rhGDNF) formulation. Methods. A combination of chromatography, peptide mapping, mass spectroscop y, and protein sequencing was used to purify and characterize the degradati on product. Circular dichroism, 1,8-ANS and heparin binding, melting temper ature determination, bioassays, and preclinical pharmacokinetic and toxicol ogy testing were performed to examine its equivalence to native rhGDNF. Results. The rhGDNF with cyclic imide at aspartic acid residue 96 showed id entical activity, structure, pharmacokinetic profile, and toxicity profile to the native rhGDNF. Conclusions. Formation of cyclic imide at aspartic acid residue 96 does not affect the pharmaceutical quality of the rhGDNF formulation.